Universität zu Köln

Vay, Sabine Ulrike, Blaschke, Stefan, Klein, Rebecca, Fink, Gereon Rudolf, Schroeter, Michael and Rueger, Maria Adele (2016). Minocycline Mitigates the Gliogenic Effects of Proinflammatory Cytokines on Neural Stem Cells. J. Neurosci. Res., 94 (2). S. 149 - 161. HOBOKEN: WILEY. ISSN 1097-4547

Full text not available from this repository.

Abstract

Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. (c) 2015 Wiley Periodicals, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vay, Sabine Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286504
DOI:	10.1002/jnr.23686
Journal or Publication Title:	J. Neurosci. Res.
Volume:	94
Number:	2
Page Range:	S. 149 - 161
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-4547
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADULT BRAIN; CEREBRAL-ISCHEMIA; INFLAMMATION; MICROGLIA; NEURONS; ACTIVATION; PRECURSORS; STROKE; MOUSE; DIFFERENTIATION Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28650